This revised Program Project Grant (PPG) application seeks an increased understanding of the relationships between dog or cat exposure during infancy and a lower risk of allergic asthma. We believe that this protective association is related to different patterns of microbial stimulation during immune development. Four synergistic Projects will examine our hypothesis that the presence of pets in a home results in a more diverse bacterial community composition (BCC) of the dust in the home which in turn influences the development of the gut BCC of a newborn infant living in the home. A more diverse gut BCC shifts the maturation of the infant's immune system such that later immune responses are less likely to produce IgE antibody responses and allergic asthma. Project 1 examines the relationships between the presence of a dog or cat in a home, the BCC of dust in the home, the BCC of stools of infants living in homes and allergic sensitization at 2 years of age. An innovative, culture-independent microarray (G3 PhyloChip) will be used to characterize the BCCs utilizing previously collected samples from the ongoing WHEALS birth cohort study. Changes in home BCC following introduction of a dog are also examined. To further examine relationships between dog exposure and immune development. Project 2 will recruit a new birth cohort of children either living with or without a dog, measure infant stool BCC, and follow the cohort with detailed studies of immune function until 18 months of age to determine the impact of dog exposure on immune maturation. Project 3 uses mouse models of allergic asthma to further examine the influence of house dust from homes with and without dogs on immune responses that result in lung inflammation. The use of mouse models allows more detailed studies of immune functions from multiple compartments of the body than are possible with human children. Project 4 again utilizes the existing WHEALS birth cohort to examine the relationships between dog or cat exposure during the first year of age, 6-month infant stool BCC, and the presence of allergic asthma at 9 years of age. The Projects are supported by five Cores which each provide essential services to all four Projects.